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Biomedical subjects

L Corey

Publications and source records attributed to L Corey.

At least 181 records · Page 10Linked to original sources
PubMed1995

Automated microneutralization: method and comparison with western blot for type-specific detection of herpes simplex antibodies in two pregnant populations.

A novel method for the detection of microneutralization was compared to Western blot for detection of type-specific antibodies to herpes simplex virus in two pregnant patient populations in Vancouver. From an unselected group of women in labor in a tertiary care obstetric hospital (426) and another group of women specially referred for assessment of genital herpes in pregnancy (195) 20 and 88%, respectively, were seropositive for herpes simplex virus type 2 antibodies by Western blot. During the study period, 93 (48%) of the high-risk group were culture positive for HSV-2 and all but one case was verified serologically by Western blot. Therefore, the sensitivity for Western blot in this high seroprevalence group was 99%. The false-negative case had longstanding recurrent infection and on retest was found to be a laboratory error. For microneutralization, type-specificity was especially difficult to distinguish among patients with mixed viral type patterns. Comparing microneutralization to Western blot as the gold standard, sensitivity, specificity, positive and negative predictive values were 84, 78, 97 and 40% respectively, for the referred group and 73, 82, 51 and 92%, respectively, for the unselected group. Poor negative and positive predictive values for the referred group and unselected populations, respectively, demonstrate that microneutralizations are not clinically acceptable for type-specific antibody detection. By contrast, serology by Western blot is very sensitive and apparently highly specific.

Antibodies, Viral↗
PubMed1995

Frequency and reactivation of nongenital lesions among patients with genital herpes simplex virus.

OBJECTIVE: To determine the frequency, recurrence patterns, and host factors associated with nongenital herpes simplex virus lesions. PATIENTS AND METHODS: In this cohort study at a referral clinic, 457 patients with first episodes of genital herpes were prospectively observed to evaluate the anatomic sites of herpetic lesions at the first and subsequent visits. Of these patients, 73 had primary genital herpes simplex virus (HSV) type 1, 326 had primary first episode genital HSV-2, and 58 had HSV-1 infection prior to acquisition of genital HSV-2. The median follow-up was 63 weeks. RESULTS: Nongenital lesions at the time of acquisition of genital herpes were observed in 25%, 9%, and 2% of patients with primary HSV-1, primary HSV-2, and nonprimary HSV-2, respectively. Half of the patients with concurrent genital and nongenital lesions subsequently had recurrences at a nongenital site. Twenty patients (6.5%) whose primary genital HSV-2 infection involved only the genitalia subsequently developed nongenital recurrences, primarily on the buttocks (12) and legs (4). Nongenital recurrences, especially buttock recurrences, tended to be less frequent but of longer duration than genital recurrences. CONCLUSIONS: Overall, 21% of patients with primary genital herpes will have or will subsequently develop a nongenital recurrence. Among patients with HSV-1, nongenital lesions tended to occur more often on the hand and face, whereas HSV-2 lesions appeared more often on the buttocks. Buttock lesions due to HSV recur less frequently but last longer than genital lesions.

Herpes Genitalis↗
PubMed1995

Herpesvirus infections in persons infected with human immunodeficiency virus.

Herpesviruses are among the most common causes of infections of humans. Viruses in this family share the unique biological property of being able to establish latency and to recur. Furthermore, chronic excretion of virus is not uncommon. In the immunocompromised host, including persons with human immunodeficiency virus (HIV) infection, herpesvirus disease can be particularly severe, resulting in chronic, persistent, active infection and, in some cases, life-threatening disease. The most pathogenic of the herpesviruses in patients with AIDS include herpes simplex viruses, human cytomegalovirus, and varicella-zoster virus. Disease caused by Epstein-Barr virus, particularly opportunistic malignancies, has been recognized. A new herpesvirus that is associated with Kaposi's sarcoma was recently described. On the other hand, disease caused by human herpesviruses 6 and 7 in persons infected with HIV remains to be unequivocally recognized. Prevention of exposure to herpesviruses, disease, and recurrence requires different measures than those for some of the other opportunistic infections in HIV-infected patients; this is because herpesvirus disease develops in most of these individuals as a result of reactivation rather than primary infection. Thus, approaches to the prevention and control of herpesvirus infections must be individualized according to both the type of virus as well as the type of infection (i.e., primary or recurrent). We discuss recommended measures for the prevention and control of these infections.

HIV Infections↗
PubMed1995

Cervical but not urinary excretion of cytomegalovirus is related to sexual activity and contraceptive practices in sexually active women.

The relationship between sexual activity and genitourinary excretion of cytomegalovirus (CMV) was evaluated in 1481 women at a sexually transmitted disease (STD) clinic. Among 951 who were CMV-seropositive, 16.6% had CMV isolated, from cervix alone in 9.4%, urine alone in 3.8%, and both sites in 4.2%. Isolation rates were highest in young women (P < .001). Compared with those with only cervical infection, women shedding from both cervix and urine were younger, began sexual activity when younger, had more recent partners, and a higher frequency of CMV-specific IgM, suggesting recent CMV infection. By logistic regression, cervical CMV excretion was associated with concomitant gonococcal infection (P = .008) and was less frequent in those using barrier contraception (P = .036). Isolated urinary excretion of CMV was not associated with sexual activity, concomitant cervical infections, or use of contraception. Cervical CMV infection is related to sexual activity, acquisition of other STDs, or exogenous reinfection, and urinary CMV is not.

Adolescent↗
PubMed1995

Seminal shedding of human immunodeficiency virus type 1 and human cytomegalovirus: evidence for different immunologic controls.

Contact with semen of seropositive men is important for sexual transmission both human immunodeficiency virus (HIV) type 1 and human cytomegalovirus (CMV), but the factors that determine shedding of either virus in semen are poorly understood. HIV was cultured from 36 (17%) of 215 semen specimens from 56 seropositive men, and CMV was cultured from 42 (30%) of 139 specimens. In logistic regression models, the CD8+ cell count in peripheral blood was the best predictor of HIV shedding in semen. Shedding of HIV was more closely associated with concomitant shedding of CMV than with CD4+ cell count, and antiretroviral therapy had minimal influence on shedding of HIV. In contrast, CD4+ cell count was the best predictor of CMV shedding in semen. Factors that determine shedding of viruses in semen may differ substantially from those that influence virus levels in the systemic immune compartment. Likewise, immunologic factors that determine shedding of HIV appear to differ from those that control shedding of CMV in semen.

Antiviral Agents↗
PubMed1995

A randomized, double-blind, placebo-controlled trial of systemically administered interferon-alpha, -beta, or -gamma in combination with cryotherapy for the treatment of condyloma acuminatum.

One hundred fifty-two patients were enrolled in a study to evaluate 3 interferon (IFN) preparations used in combination with cryotherapy for treatment of anogenital warts. Subjects received subcutaneous injections (2 x 10(6) units/m2) of IFN-alpha n1, -beta, -gamma or placebo 3 times a week for 6 weeks and cryotherapy with liquid nitrogen. Subjects were followed < or = 1 year. Among patients followed > or = 12 weeks, two-thirds had a complete response. No significant differences in rates of complete response (P = .37) or reappearance of a wart at the initial site (P = .20) were noted among the treatment groups. However, patients who received IFN-beta or -gamma developed new warts at a significantly lower frequency (P = .02). IFN administration was associated with side effects but was well tolerated. IFN-beta was the least toxic of the 3 preparations and had the best therapeutic ratio.

Adult↗
PubMed1995

Infection of Macaca nemestrina brain with human immunodeficiency virus type 1.

We previously reported that pigtailed macaques (Macaca nemestrina) became infected after intravenous inoculation with the LAI strain of human immunodeficiency virus type 1 (HIV-1), an isolate that replicates in both M. nemestrina lymphocytes and blood-derived monocyte/macrophages. In the current study we investigated the presence of HIV-1 and pathology in the postmortem brains of four of these macaques. Histopathological findings revealed focal lesions in white matter in the frontal and occipital lobes of one macaque, with myelin loss, nerve fibre loss, and gliosis within these lesions. Semi-quantitative, solution-based PCR revealed HIV-1 DNA in the brains of two of the other macaques. Using slide-based PCR-driven in situ hybridization, we studied these two macaques further and detected intranuclear, circular HIV-1 DNA in vascular endothelia and other non-neuronal brain cells. These findings indicate that M. nemestrina brain can be infected with HIV-1 in vivo and may provide a useful animal model for understanding early HIV-1 brain infection in humans.

AIDS Dementia Complex↗
PubMed1995

Cytotoxic and proliferative T cell responses in HIV-1-infected Macaca nemestrina.

Macaca nemestrina has been described as an animal model for acute HIV-1 infection. This animal, unlike most infected humans, appears to contain HIV-1 replication. Therefore analysis of HIV-1-specific proliferative and cytotoxic T lymphocyte (CTL) responses following HIV-1 challenge of M. nemestrina may provide information into the role of such responses in both the control of acute HIV infection and protective immunity. Although CD4+ T cell responses to HIV-1 are generally difficult to detect in HIV-1-infected humans, early and persistent CD4+ T cell proliferative responses to HIV-1 antigens were detected in all HIV-1-inoculated M. nemestrina. HIV-1-specific CD8+ CTL responses were evaluated in PBMC by stimulation with autologous cells expressing HIV-1 genes, limiting dilution precursor frequency analysis, and T cell cloning. CTL reactive with gag, env, and nef were present 4-8 wk after infection, and persisted to 140 wk after infection. The presence of both CD4+ and CD8+ T cell responses before and after clearance of HIV-1 viremia is consistent with a role for these responses in the successful control of HIV-1 viral replication observed in M. nemestrina. Further studies of T cell immunity in these animals that resist disease should provide insights into the immunobiology of HIV-1 infection.

Animals↗
PubMed1995

Persistent hepatitis C virus infection after liver transplantation: clinical and virological features.

We report a prospective clinical and virological study of 18 patients undergoing orthotopic liver transplantation, selected because of hepatitis C virus (HCV) RNA positivity before transplantation. Nine of the 18 patients (50%) developed chronic active hepatitis (CAH) in liver allografts during the first year posttransplantation; hepatitis was first observed between 6 and 25 weeks posttransplantation. HCV viremia was measured for all patients before transplantation and on posttransplantation days 3, 7, and 14, and months 1, 6, 12, and 24 to 41, by quantitative competitive RNA polymerase chain reaction (QC-PCR). HCV RNA levels on posttransplantation days 3, 7, and 14 were significantly higher among patients who subsequently developed CAH versus those who did not (P < .02 by t-test and Mann-Whitney test on all three dates). However, HCV RNA levels in sera obtained at 1, 6, and 12 months posttransplantation did not correlate with CAH at 1 year or with HCV genotype determined in posttransplantation sera. At least two serial liver biopsy specimens from each patient were stained for HCV nonstructural 4 (NS4) antigen by immunohistochemistry. The intensity of cytoplasmic staining of NS4 antigen was significantly higher for specimens with CAH versus those without CAH (P = .028 by chi 2). Three patients developed bridging fibrosis in liver allografts during the first year after transplantation; all three patients had intense (3+) immunostaining for NS4 antigen, and the infecting genotypes were 1a, 1b, and 1a plus 1b, respectively. In summary, the 18 patients all developed high-titer viremia by 1 month after liver transplantation, whereas CAH developed in 50% of allografts during the first year after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic Disease↗
PubMed1995

Intermittent shedding of human immunodeficiency virus in semen: implications for sexual transmission.

PURPOSE: We attempt to increase our understanding of human immunodeficiency virus (HIV) shedding in semen. MATERIALS AND METHODS: We followed 16 seropositive men for up to 27 months by HIV cocultivation, with a subset evaluated using the polymerase chain reaction. RESULTS: The proportion with at least 1 HIV positive semen culture increased from 3 of 16 subjects (19%) at visit 1 to 10 (63%) by visit 5. Overall, HIV was cultured from 25 of 114 specimens (22%). Shedding was intermittent for each of the 10 men with at least 1 positive culture and seminal shedding patterns were highly variable. CONCLUSIONS: By culture and polymerase chain reaction, HIV is shed intermittently in the semen. If cultures are performed often enough most seropositive men shed HIV in the semen.

Base Sequence↗
PubMed1994

Recurrence rates in genital herpes after symptomatic first-episode infection.

OBJECTIVE: To evaluate the frequency of reactivation of genital herpes infection and to identify predictors for recurrence. DESIGN: Prospective, observational cohort study. SETTING: Research clinic. PATIENTS: 457 consecutive patients who did not have acute-phase serum antibodies to herpes simplex virus type 2 (HSV-2) but who did have herpes simplex virus (HSV) isolated from genital lesions. RESULTS: Eighty-nine percent of patients with HSV-2 had at least one recurrence during follow-up (median, 391 days); the median monthly recurrence rate was 0.34. Thirty-eight percent had at least 6 recurrences during the first year and 20% had more than 10 recurrences. The median monthly recurrence rate was 0.43 for men and 0.33 for women (difference, 0.10 [95% CI, 0.03 to 0.19]; P < 0.01). Twenty-six percent of women and 8% of men had no or 1 recurrence in year 1 of follow-up, whereas 14% of women and 26% of men had more than 10 recurrences. Patients who had severe primary HSV-2 infection (duration, > or = 35 days) had recurrences nearly twice as often (0.66 compared with 0.36 recurrences per month [95% CI, 0.18 to 0.57]) and had a shorter time to first recurrence when compared with those who had shorter first episodes. CONCLUSIONS: Almost all persons with initially symptomatic HSV-2 infection have symptomatic recurrences. More than 35% of such patients have frequent recurrences. Recurrence rates are especially high in persons with an extended first episode of infection, regardless of whether they receive antiviral chemotherapy with acyclovir. Men with genital HSV-2 infection have about 20% more recurrences than do women, a factor that may contribute to the higher rate of HSV-2 transmission from men to women than from women to men and to the continuing epidemic of genital herpes in the United States.

Acyclovir↗
PubMed1994

Antibody to herpes simplex virus type 2 as serological marker of sexual lifestyle in populations.

OBJECTIVES: To examine the epidemiology of antibody to herpes simplex virus type 2 and to assess its suitability as a serological marker of sexual behaviour in populations with high and low prevalences. DESIGN: Cross sectional survey. SETTING: Department of genitourinary medicine and blood donation centre in central London. SUBJECTS: Representative sample of 869 patients attending department between November 1990 and December 1991, and 1494 consecutive blood donors attending for donation between February and April 1992. METHOD: Participants had a blood sample taken for antibody testing with a novel type specific assay and completed a questionnaire. RESULTS: Prevalence of antibody differed significantly between the two groups (188/833 (22.7%) clinic attenders; 102/1347 (7.6%) blood donors). In both populations antibody was strongly associated with sex, sexual orientation, years of sexual activity, number of lifetime sexual partners, and past infection with sexually transmitted diseases after other factors were controlled for. Only 130 (45%) of all those with antibody had symptoms suggestive of genital herpes, and 79 (27.4%) had had genital herpes diagnosed. Of those without antibody to herpes simplex viruses type 1 and 2, 8.0% reported genital blisters or sores and 1.1% had had genital herpes diagnosed by a doctor. CONCLUSIONS: The strong relation between herpes simplex virus type 2 and sexual lifestyle suggests that the presence of antibody to the virus may be suitable for use as an objective, serological marker of patterns of sexual behaviour in different populations. These data show that only a minority of those infected with herpes simplex virus type 2 have a diagnosis of genital herpes or express clinical symptoms, making serological determinants of infection essential for epidemiological studies.

Adolescent↗
PubMed1994

Interpreting HIV serodiagnostic test results in the 1990s: social risks of HIV vaccine studies in uninfected volunteers. NIAID AIDS Vaccine Clinical Trials Group.

OBJECTIVE: To evaluate the influence of a human immunodeficiency virus (HIV) vaccine given to uninfected volunteers on the interpretation of serodiagnostic HIV test results. DESIGN: Retrospective cohort study. SETTING: 5 AIDS Vaccine Evaluation Units funded by the National Institute of Allergy and Infectious Diseases. PARTICIPANTS: The first 266 healthy adult volunteers (aged 18 to 60 years) who did not have HIV infection and whose history suggested that they were at low risk for acquiring HIV infection. MEASUREMENTS: HIV antibody was measured by enzyme-linked immunosorbent assay (ELISA) and Western blot test, the results of which were interpreted on the basis of four different published criteria. RESULTS: At some time during the first 12 months of the vaccine studies, 68% of volunteers were positive for HIV antibodies by ELISA. Depending on criteria used to interpret Western blot test results, 0% to 44% of volunteers had positive results that might have caused them to be incorrectly labeled as HIV infected. CONCLUSIONS: Significant social risks to volunteers participating in HIV vaccine studies were identified. Persons interpreting HIV serodiagnostic test results must consider that an HIV vaccine can cause a positive result in persons who are not infected.

AIDS Vaccines↗
PubMed1994

NIH conference. HIV vaccine development: a progress report.

The development of a safe, effective preventive vaccine for human immunodeficiency virus (HIV) infection remains an area of vigorous research. Several highly innovative vaccine candidates are being developed, and more than 13 vaccine candidates have been tested in human phase I or II trials. All have produced antibody and several have produced modest neutralizing titers, but to date no reproducible evidence has suggested prolonged, high-titer neutralization across a diversity of HIV strains. Furthermore, only the live recombinant vector approaches have produced some evidence of cytotoxic T-cell responses. The principal obstacle to progress is the lack of definitive information on what constitutes a protective immune response. There is no animal model for HIV-induced disease. Hence, the identification of the correlates of immunity and more useful animal models is among the highest priorities for HIV vaccine research. Large-scale efficacy trials raise daunting scientific, ethical, and resource issues. Nonetheless, preparation in such trials is underway in order to be in a position to evaluate the most promising vaccine candidate.

AIDS Vaccines↗
PubMed1994

Frequent detection of genital herpes simplex virus DNA by polymerase chain reaction among pregnant women.

OBJECTIVE: To investigate the prevalence and level of genital herpes simplex virus (HSV) among women at delivery. DESIGN, PATIENTS, AND SETTING: A prospective analysis of HSV by culture and by polymerase chain reaction (PCR) of genital specimens and by HSV serologic studies in 100 asymptomatic women in labor; prospective analysis of HSV by PCR among 50 seronegative nonpregnant women at a student health center; and retrospective analysis of genital specimens for HSV by PCR from 17 HSV culture-positive women with uninfected neonates and from two HSV culture-negative women with HSV-infected neonates. All pregnant women were at a university hospital. MAIN OUTCOME MEASURES: Presence of HSV by culture and levels of HSV by quantitative, type-specific PCR in cervical and vulvar specimens; HSV serologic testing by Western blot. RESULTS: All of the 100 asymptomatic women in labor who were studied prospectively were HSV culture negative. In nine HSV was recovered by PCR. Herpes simplex virus was recovered by PCR in one of the 50 seronegative nonpregnant women; she soon became seropositive. All 17 culture-positive women had HSV recovered by PCR. High levels of HSV DNA were obtained by PCR from the two culture-negative women with infected neonates. Among those from whom HSV was recovered by PCR, HSV DNA levels were 250 times higher from culture-positive samples than from culture-negative samples (11,571 genome equivalents vs 46 genome equivalents; P < .001). CONCLUSIONS: The frequency of infant exposure to HSV DNA-containing secretions from HSV-seropositive mothers is about eight times higher than previously reported using HSV culture methods. High maternal levels of HSV DNA may be associated with an increased frequency of transmission of HSV to the infant.

Base Sequence↗
PubMed1994

Placebo-controlled trial of vaccination with recombinant glycoprotein D of herpes simplex virus type 2 for immunotherapy of genital herpes.

Immunotherapy of chronic viral diseases with vaccines is an important but unproven concept. We investigated the effect of a vaccine containing recombinant glycoprotein D (gD2) of herpes simplex virus type 2 (HSV-2) on the frequency of symptomatic outbreaks in patients with genital herpes. 98 patients with documented genital herpes who reported 4-14 recurrences per year were enrolled in a double-blind, placebo-controlled trial. Subjects received injections of either 100 micrograms gD2 in alum or alum alone (placebo) at 0 and 2 months, and recurrences were documented for 1 year. The vaccine was well tolerated. gD2 recipients reported fewer recurrences per month than placebo recipients (mean 0.42 [SE 0.05] vs 0.55 [0.05]; p = 0.055), had fewer virologically confirmed recurrences per month (0.18 [0.03] vs 0.28 [0.03]; p = 0.019), and had a lower median number of recurrences for the study year (4 [range 0-17] vs 6 [0-15]; p = 0.039). Neither genital recurrence nor the placebo vaccine had any discernible effect on HSV-2-specific antibody responses, but gD2 vaccine boosted neutralising antibodies to HSV-2 fourfold and gD2-specific titres sevenfold over baseline levels. These results inspire optimism about the potential use of vaccine for the treatment of chronic, recurring viral diseases.

Adult↗